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Calcineurin inhibition prevents calpain‐mediated proteolysis of tau in differentiated PC12 cells
Author(s) -
Xie Hanqing,
Johnson Gail V.W.
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19980715)53:2<153::aid-jnr4>3.0.co;2-6
Subject(s) - dephosphorylation , okadaic acid , calpain , calcineurin , chemistry , phosphatase , phosphorylation , proteolysis , biochemistry , microbiology and biotechnology , calcium , biology , medicine , enzyme , organic chemistry , transplantation
The effects of calcium influx on tau levels and phosphorylation were examined in differentiated PC12 cells. Maitotoxin‐induced calcium influx resulted in time‐ and concentration‐dependent tau dephosphorylation and degradation. Incubation of PC12 cells with a membrane‐permeable calpain inhibitor blocked maitotoxin‐induced tau degradation, suggesting the involvement of calpain in calcium‐stimulated tau turnover. Okadaic acid or the calcineurin inhibitor FK520 partially inhibited maitotoxin‐induced tau dephosphorylation at the Tau‐1 epitope, indicating both phosphatase 2A/1 and calcineurin were involved. In addition, FK520, but not okadaic acid, blocked the maitotoxin‐induced tau degradation, demonstrating that dephosphorylation of specific tau epitopes by was essential for calpain‐mediated tau degradation. Moreover, maitotoxin effects were likely independent of tau association with microtubules because maitotoxin induced tau degradation and dephosphorylation in the presence of either nocodazole or taxol. These data provide evidence that calpain is involved in tau turnoverin situand calcineurin plays an important role in modulating tau susceptibility to calpain. J. Neurosci. Res. 53:153–164, 1998. © 1998 Wiley‐Liss, Inc.